November 30, 2017
2 min read

Beyond 25-(OH)D, vitamin D metabolite ratio may better predict hip fracture risk

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

Charles Ginsberg
Charles Ginsberg

Among older adults, a lower 24,25-dihydroxyvitamin D to 25-hydroxyvitamin D ratio, also known as the vitamin D metabolic ratio, is a stronger predictor of hip fracture risk than 25-(OH)D measurement alone, according to study data published in Bone.

Recent studies suggest that assessing vitamin D status based on concentrations of 25-(OH)D alone may be suboptimal, and past studies evaluating the relationship among 25-(OH)D, bone density and fractures reported mixed findings, Charles Ginsberg, MD, of the VA San Diego Healthcare System, and colleagues wrote in the study background.

“Additionally, it is unclear how well the serum concentration of 25-(OH)D reflects the downstream effects of vitamin D receptor signaling in response to 1,25-(OH)2D binding, as 25-(OH)D may be activated, catabolized or remain in an inactive form,” Ginsberg and colleagues wrote. “Furthermore, assays for 25-(OH)D are affected by concentration of vitamin D-binding protein, which can vary between individuals, and may not reflect bioavailable 25-(OH)D. Alternative markers have been proposed.”

Ginsberg and colleagues analyzed data from 890 randomly selected patients aged at least 65 years participating in the Cardiovascular Health Study, a community-based, longitudinal observational cohort study that began enrollment in 1989 (mean age, 78 years; 60% women; 16% black). Blood samples provided at the 1996-1997 examination served as the baseline data for this study. Researchers assessed measurements of serum parathyroid hormone (PTH) and the vitamin D metabolites 25-(OH)D2, 25-(OH)D3 and 24,25-(OH)2D3, as well as total hip bone mineral density data measured at the 1994-1995 study visit (n = 358). To evaluate longitudinal risk for incident hip fracture, researchers used a case-cohort design, identifying participants from the overall study cohort who sustained hip fractures after the baseline 1996-1997 study visit (n = 214) and comparing their vitamin D metabolite measurements with those of the 75 patients who sustained hip fractures in the randomly selected cohort. Researchers used linear regression analyses to evaluate the association between vitamin D measurements and BMD, and used Prentice-weighted Cox models to evaluate the association between vitamin D measurements and incident hip fracture.

Within the cohort, the mean 25-(OH)D concentration was 28 ng/mL; 58% had levels of 30 ng/mL or less. The mean 24,25-(OH)2D concentration was 1.7 ng/mL, and the mean vitamin D metabolic ratio was 6.84 (ng/mL)/(ng/mL).

In adjusted models, researchers found that each 1% higher 25-(OH)D, 24,25-(OH)2D and vitamin D metabolite ratio measurement were associated with a 0.32%, 0.25% and 0.26% lower PTH measurement, respectively. Among the 358 participants with BMD measurement data, researchers did not observe any associations between BMD, 25-(OH)D and vitamin D metabolite ratio measurements; however, a higher 24,25-(OH)2D measurement was associated with a modestly higher BMD.

In the case-cohort analysis for hip fracture risk, researchers did not observe an association between 25-(OH)D and risk for hip fracture. However, each standard deviation increase in 24,25-(OH)2D was associated with a 27% lower risk for hip fracture in adjusted models. Similarly, each standard deviation increase in vitamin D metabolite ratio was associated with a 26% lower risk for hip fracture.

Race did not modify any of the interactions, according to researchers.

“We found that a lower vitamin D metabolite ratio strongly predicted risk of hip fracture in this cohort, while 25-hydroxyvitamin D did not,” Ginsberg told Endocrine Today. “Thus, the vitamin D metabolite ratio may provide additional insights into bone health beyond measurement of 25-hydroxyvitamin D alone. Future studies are needed to determine how to change the vitamin D metabolite ratio and if increasing the it will help prevent fractures.”– by Regina Schaffer

For more information:

Charles Ginsberg, MD, can be reached at

Disclosures: The authors report no relevant financial disclosures.